The present invention includes a method and compositions for preventing primary or acquired resistance of epidermal growth factor receptors (EGFR) inhibitors in a cancer with deregulated EGFR comprising: identifying a subject suspected of needing treatment for primary or acquired resistance to epidermal growth factor receptor (EGFR) inhibitors of the cancer with deregulated EGFR； and providing the subject with a therapeutically effective amount of a chromosome region maintenance 1 (CRM1) inhibitor and an inhibitor of EGFR in an amount sufficient to reduce or eliminate the cancer.
